Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, clinical trials, Lymphoid Leukemias, ALL, Acute Myeloid Malignancies, AML, Biological therapies, APL, Clinical Research, Diseases, Therapies, Immunotherapy, Lymphoid Malignancies, Myeloid Malignancies, Transplantation
Methods: Standard of care reduced-intensity flu/cy/TBI conditioning was followed by an unmanipulated bone marrow graft and 50mg/m2 Cy on days +3 and +4 post-transplant. EAGD were manufactured using the Miltenyi Prodigy bioreactor and cryopreserved. The product was infused intravenously within 5 days of neutrophil engraftment (ANC >500/µL X 3d). Peripheral blood was collected at EAGD infusion and monthly thereafter through day +90, with additional collections every 6 months through 1 year. Biologic parameters included multiparameter flow cytometric immunophenotyping and single cell cytokine analysis of the EAGD graft. Peripheral blood analysis includes leukocyte count and differential, immunophenotyping, and serum Th1/Th2/Th17 cytokine analysis. Primary endpoints include dose-limiting toxicities (DLT) and grade 3-4 adverse events while secondary endpoints include incidence of acute and chronic GvHD, relapse, and overall survival.
Results: Three patients have received the first dose level of 1 x 106 EAGD/kg. All three patients remain in morphologic complete remission at 26.5, 24.2, and 12.5 months post-BMT. One patient is receiving ongoing hypomethylating therapy for the occurrence of recipient chimerism. Grade 1-2 toxicities include constipation, CMV reactivation, emesis, fatigue, and hypomagnesaemia. Steroid-responsive cutaneous acute Grade I-II GVHD has been observed in all patients with one patient experiencing Grade II intestinal GvHD. No chronic GVHD, DLTs, treatment-related ≥ grade 3 adverse events, or cytokine release syndrome has occurred. EAGD grafts contained 88.7% - 99.2% Vγ9Vδ2+ γδ T cells with small populations of NK cells and <1.0 x 10 αβ T cells/kg. EAGD principally expressed Granzyme B, MIP1α, MIP1β, and IL-2.
Significant peripheral lymphodepletion persisted through the first 100 days post-BMT followed by slow recovery of CD4+, CD8+, γδ T and B cells. NK cells remained within the low normal range throughout. T cells transitioned from a CD45+CD27- effector phenotype to CD45RA CD27 central to effector memory phenotype as recovery progressed. CD3 CD4 CD25 FoxP3 Treg cells remained <3% of circulating T cells. Preliminary serum cytokine and chemokine analysis revealed predominant expression of IFNγ, IL-12p70, IP-10, RANTES and TNFα.
Conclusions: Early indications suggest that EAGD transfusion with the initial dose level of 1 x 106 EAGD/kg has manageable toxicity and an appropriate immune recovery profile with 3 of 3 patients alive and progression-free.
Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT03533816
Disclosures: McGuirk: Sana: Honoraria; CRISPR Therapeutics: Consultancy; In8bio, Inc.: Other: IIT Clinical Trial; Novartis: Consultancy, Honoraria; Orca Bio: Research Funding; BMS: Consultancy, Honoraria, Speakers Bureau; Nextar: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Allovir: Consultancy, Honoraria, Research Funding, Speakers Bureau; Juno Therapeutics: Consultancy, Honoraria, Research Funding. Abhyankar: Talaris: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Research Funding, Speakers Bureau; Therakos: Consultancy, Research Funding, Speakers Bureau. Goswami: IN8Bio, Inc.: Current Employment. ter Haak: IN8Bio, Inc.: Current Employment. Youngblood: IN8Bio, Inc.: Current Employment. Lamb: IN8Bio, Inc.: Current Employment.
See more of: Oral and Poster Abstracts